ALKENE AZETIDINE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS

摘要

The present invention relates to alkene azetidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.

主权项

1. A compound represented by Formula I, or an E geometric isomer, or a Z geometric isomer, or a mixture of an E and a Z geometric isomers, or an enantiomer, or a diastereoisomer, or a tautomer, or a zwitterion, or a pharmaceutically acceptable salt thereof: wherein: A is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl; B is optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl or optionally substituted C3-8 cycloalkenyl; R1 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl; R2 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl; R3 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl; R4 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C (O)R11, NR12R13 or hydroxyl; R5 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl; R6 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, NR12R13 or hydroxyl; R7 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl; R8 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl; R9 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl; R10 is H, halogen, —OC1-8 alkyl, optionally substituted C1-8 alkyl, CN, C(O)R11, optionally substituted C6-10 aryl, optionally substituted heterocycle, optionally substituted C3-8 cycloalkyl, optionally substituted C3-8 cycloalkenyl, NR12R13 or hydroxyl; L1 is O, S, S(O), NH or CH2; L2 is O, S or CHR12, R11 is OH or optionally substituted C1-8 alkyl; a is 1, 2, 3, 4, 5 or 6; R12 is H or optionally substituted C1-8 alkyl; and R13 is H or optionally substituted C1-8 alkyl.